Developments in transgenic animal research, together with the limited success of gene transfers targeting human somatic cells, have triggered renewed interest in research on germ line interventions in humans. Debates over modifying the human germ line tend to focus on the longterm consequences to society. Comparatively little attention is paid to the human research that will be necessary to establish that genetic interventions are safe and effective. The aim of this project is to apply U.S. policies governing research involving human participants - and the ethical principles underlying such policies - to studies of germ line interventions. In the project, a Core Group of experts in genetics and research ethics and policy will consider how policy provisions and ethical principles would bear on research proposals to alter the genome of a human embryo when the goal is to allow that embryo to develop into a child. The Core Group will receive information and guidance from scientific consultants with expertise in human and animal genetics. Project participants will prepare materials to inform investigators, local and national oversight bodies, and the interested public about the ethical and policy complexities of conducting research altering the genotype of human embryos. Project participants will also: (1) develop guidelines for applying federal policy governing research involving human subjects to germ line studies; and (2) consider additional rules and procedures that may be warranted to ensure that subjects are adequately protected in the research process. The project will yield two manuscripts, one aimed at a general audience and a more detailed monograph for groups asked to evaluate the ethical and regulatory acceptability of proposals to conduct germ line research in humans.